A HT/PEXEL motif in Toxoplasma dense granule proteins is a signal for protein cleavage but not export into the host cell.
A HT/PEXEL motif in Toxoplasma dense granule proteins is a signal for protein cleavage but not export into the host cell.
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DOI：
10.1111/tra.12049
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Knoll LJ
中科院分区：
文献类型：
--
作者：
Hsiao CH;Luisa Hiller N;Haldar K;Knoll LJ
顶端复合体寄生虫，如刚地弓形虫和疟原虫，分泌蛋白质附着、入侵和调节宿主细胞。宿主靶向（host targeting， HT），也被称为疟原虫输出元件（Plasmodium export element， PEXEL），它将疟原虫蛋白引导到红细胞中，重塑宿主细胞并建立感染。弓形虫的生物信息学分析显示，在几种假设未知的致密颗粒蛋白的n端存在HT/ pesel样基序。血凝素（HA）标记的这些未表征的蛋白与寄生液泡膜（PVM）上的致密颗粒蛋白共定位。与疟原虫不同的是，这些含有HT/PEXEL蛋白的弓形虫不会输出到宿主细胞中。对弓形虫HT/PEXEL基序RxLxD/E的定点诱变表明，精氨酸和亮氨酸残基可用于蛋白质切割。HT/PEXEL基序内的突变阻止了蛋白质的切割，仍然允许靶向PV，但蛋白质与PVM的相关性降低。在切割位点前后添加Myc标签表明加工过的HT/PEXEL蛋白增加了PVM关联。这些发现表明，虽然弓形虫和疟原虫具有相似的HT/PEXEL基序，但弓形虫HT/PEXEL蛋白与PVM相互作用，但不交叉。
Apicomplexan parasites, such as Toxoplasma gondii and Plasmodium, secrete proteins for attachment, invasion and modulation of their host cells. The host targeting (HT), also known as the Plasmodium export element (PEXEL), directs Plasmodium proteins into erythrocytes to remodel the host cell and establish infection. Bioinformatic analysis of Toxoplasma revealed a HT/PEXEL-like motif at the N-terminal of several hypothetical unknown and dense granule proteins. Hemagglutinin (HA)-tagged versions of these uncharacterized proteins show co-localization with dense granule proteins found on the parasitophorous vacuole membrane (PVM). In contrast to Plasmodium, these Toxoplasma HT/PEXEL containing proteins are not exported into the host cell. Site directed mutagenesis of the Toxoplasma HT/PEXEL motif, RxLxD/E, shows that the arginine and leucine residues are permissible for protein cleavage. Mutations within the HT/PEXEL motif that prevent protein cleavage still allow for targeting to the PV but the proteins have a reduced association with the PVM. Addition of a Myc tag before and after the cleavage site shows that processed HT/PEXEL protein has increased PVM association. These findings suggest that while Toxoplasma and Plasmodium share similar HT/PEXEL motifs, Toxoplasma HT/PEXEL containing proteins interact with but do not cross the PVM.
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影响因子：
64.8
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